Variant chr19-54727771-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_153443.5(KIR3DL3):c.516C>T(p.His172His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,613,464 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 7 hom., cov: 30)

Exomes 𝑓: 0.012 ( 137 hom. )

Consequence

KIR3DL3
NM_153443.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

KIR3DL3 (HGNC:16312): (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 3) Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. This gene is one of the "framework" loci that is present on all haplotypes. [provided by RefSeq, Jul 2008]

KIR3DL3 links:

ENSG00000215765 (HGNC:):

ENSG00000215765 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 19-54727771-C-T is Benign according to our data. Variant chr19-54727771-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650458.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIR3DL3	NM_153443.5 link	c.516C>T	p.His172His	synonymous_variant	4/8	ENST00000291860.2	NP_703144.3	A0A8I5QEB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIR3DL3	ENST00000291860.2 link	c.516C>T	p.His172His	synonymous_variant	4/8	1	NM_153443.5	ENSP00000291860.1		A0A8I5QEB2
ENSG00000215765	ENST00000400864.3 link	n.35+3241C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00905

AC:

1372

AN:

151546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00288

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.00638

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00961

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00772

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

182526

Hom.:

AF XY:

0.0000203

AC XY:

AN XY:

98374

show subpopulations

Gnomad AFR exome

AF:

0.0000709

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0117

AC:

17066

AN:

1461800

Hom.:

137

Cov.:

AF XY:

0.0114

AC XY:

8294

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0115

Gnomad4 FIN exome

AF:

0.00930

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.00905

AC:

1372

AN:

151664

Hom.:

Cov.:

AF XY:

0.00901

AC XY:

667

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.00287

Gnomad4 AMR

AF:

0.00637

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.000200

Gnomad4 SAS

AF:

0.00962

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00764

Alfa

AF:

0.00860

Hom.:

Bravo

AF:

0.00870

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

KIR3DL3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.2

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over